Bioenergetics in human tongue pre-cancerous dysplastic oral keratinocytes and squamous cancer cells

In an endeavor to understand the metabolic phenotype behind oral squamous cell carcinomas, we characterized the bioenergetic profile of a human tongue derived cancer cell line (SCC-4 cells) and compared this profile to a pre-cancerous dysplastic oral keratinocyte (DOK) cell line also derived from human tongue. The human SCC-4 cancer cells had greater mitochondrial abundance but lower mitochondrial oxygen consumption rates than DOK cells. The lower oxygen consumption rate in SCC-4 cells can be partially explained by lower NADH-related enzymatic activity and lower mitochondrial complex 1 activity when compared to pre-cancerous DOK cells. In addition, SCC-4 cells have greater extracellular acidification rate (an index of glycolytic flux) when compared to DOK cells. In addition, treatment with recombinant human IL-6 (rhIL-6), known to drive anoikis resistance in SCC-4 cells but not DOK cells, impairs oxygen consumption in SCC-4 but not DOK cells, without affecting mitochondrial abundance. We conclude that SCC-4 cells have a less oxidative phenotype compared to DOK cells and that IL-6 attenuates mitochondrial function in SCC-4 cells while increasing glycolytic flux.